Abstract
Hydrogels were synthesized as the drug reservoir matrix for peptide-based pharmaceuticals, and the iontophoretic release and transdermal delivery of three model peptides, insulin, calcitonin, and vasopressin, from these hydrogel-based iontotherapeutic devices were investigated. The swelling behavior of polyacrylamide-type hydrogel as a function of its monomer and cross-linker concentration was studied, and a hydrogel with minimal swelling was synthesized. The release of peptides from the hydrogel matrix was found to follow a Q vs t 1/2 relationship under passive diffusion conditions, which shifted to a Q vs t relationship under iontophoresis-facilitated transport. The release flux (dQ/dt) of peptides was observed to decline when the electric current was turned off and was resumed when the current was turned on, thus allowing for modulation of drug release by varying the application parameters of iontophoresis-facilitated transport. The permeability coefficients for these peptides across the hairless rat skin were evaluated using the hydrogel formulations prepared from polyacrylamide, p-HEMA, and carbopol. A rank order of vasopressin > calcitonin > insulin was obtained in accordance with the order of molecular size.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
H. Choi, G. L. Flynn, and G. L. Amidon. Transdermal delivery of bioactive peptides: The effect of n-decylmethylsulfoxide, pH, and inhibitors on enkephalin metabolism and transport. Pharm. Res. 7:1099–1106 (1990).
D. Parasrampuria and J. Parasrampuria. Percutaneous delivery of proteins and peptides using iontophoretic techniques. J. Clin. Pharm. Ther. 16:7–17 (1991).
Y. B. Bannon, J. Corish, and O. I. Corrigan. Iontophoretic transport of model compounds from a gel matrix across a cellophane membrane, Drug Dev. Ind. Pharm. 13(14):2617–2630 (1987).
R. Groning. Electrophoretically controlled dermal or transdermal application systems with electronic indicators. Int. J. Pharm. 36:37–40 (1987).
G. Szepesi and M. Gazdag. Improved high-performance liquid chromatographic method for the analysis of insulins and related compounds. J. Chromatogr. 218:597–602 (1981).
Y. W. Chien, K. J. Li, J. C. Liu, W. M. Shi, O. Siddiqui, and Y. Sun. Iontotherapeutic device and process and iontotherapeutic unit dose. U.S. Patent 5,042,975, Aug. 27 (1991).
J. Kost and R. Langer. Equilibrium swollen hydrogels in controlled release applications. In N. A. Peppas (ed.), Hydrogels in Medicine and Pharmacy. Vol. III. Properties and Applications, CRC Press, Boca Raton, FL, 1987, pp. 95–108.
M. F. Refojo. Vapor pressure and swelling pressure of hydrogels. In J. D. Andrale (ed.), Hydrogels for Medical and Related Applications, ACS Symposium Series, Vol. 31, ACS, Washington, DC, 1976.
S. Hosaka, H. Ozawa, and H. Tanzawa. Controlled release of drugs from hydrogel matrices. J. Appl. Pol. Sci. 23:2089–2098 (1979).
R. W. Baker and H. K. Lonsdale. Controlled release: Mechanisms and rates. In A. C. Tanquary and R. E. Lacey (eds.), Controlled Release of Biologically Active Agents, Plenum Press, New York, 1974, p. 15.
B. Kari. Control of blood glucose levels in alloxan-diabetic rabbits by iontophoresis of insulin. Diabetes 35:217–221 (1986).
L. Wearley, J. C. Liu, and Y. W. Chien. Iontophoresis-facilitated transdermal delivery of Verapamil II. Factors affecting the reversibility of skin permeability. J. Cont. Release 9:231–242 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Banga, A.K., Chien, Y.W. Hydrogel-Based lontotherapeutic Delivery Devices for Transdermal Delivery of Peptide/Protein Drugs. Pharm Res 10, 697–702 (1993). https://doi.org/10.1023/A:1018955631835
Issue Date:
DOI: https://doi.org/10.1023/A:1018955631835